Hypothyroid women have persistently higher oxidative stress compared to healthy controls

• Published in: European thyroid journal Vol. 12; no. 6; pp. 1 - 10
• Main Authors: Riis, Kamilla Ryom, Larsen, Camilla, Medici, Bjarke Røssner, Jensen, Christian Zinck, Winther, Kristian H, Larsen, Emil List, Ellervik, Christina, la Cour, Jeppe Lerche, Hegedus, Laszlo, Brix, Thomas Heiberg, Poulsen, Henrik Enghusen, Knop, Filip K, Nygaard, Birte, Bonnema, Steen Joop
• Format: Journal Article
• Language: English
• Published: Bristol Bioscientifica Ltd 01.12.2023; Bioscientifica
• Subjects: 8-oxo-7 8- dihydroguanosine; 8-oxo-7 8-dihydro-2′- deoxyguanosine; 8-oxodg; 8-oxoguo; hypothyroidism; oxidative stress
• ISSN: 2235-0640; 2235-0802
• DOI: 10.1530/ETJ-23-0167

Objective: Some studies suggest that hypothyroidism is associated with increased oxidative stress. Urinary excretion of 8-oxo-7,8-dihydroguanosine (8-oxoGuo) and 8-oxo-7,8-dihydro-2’-deoxyguanosine (8-oxodG) represent whole-body RNA and DNA oxidation, respectively. These biomarkers have only been explored sparsely in patients with thyroid disorders. Methods: In forty-five Danish women with newly diagnosed hypothyroidism, we compared 8-oxoGuo and 8-oxodG before or shortly after initiating levothyroxine with the excretion rates at euthyroidism. Also, we compared the excretion of 8-oxoGuo and 8-oxodG in the patients after restored euthyroidism with eighteen healthy control subjects. Results: Compared with baseline, none of the biomarkers changed significantly in the patients after becoming euthyroid. The geometric mean of 8-oxoGuo was 1.63 (95%CI:1.49-1.78) nmol/mmol creatinine at baseline and 1.67 nmol/mmol (95%CI:1.53-1.83) at euthyroidism (p=0.39), while 8-oxodG was 1.28 nmol/mmol creatinine (95%CI:1.14-1.44) and 1.32 nmol/mmol (95%CI:1.18-1.48), respectively (p=0.47). The relative mean differences were 0.97 (95%CI:0.91-1.04) for 8-oxoGuo and 0.97 (95%CI:0.88-1.06) for 8-oxodG. At baseline, multiple linear regression revealed a positive association between free thyroxine and both biomarkers (8-oxoGuo, p<0.001; 8-oxodG, p=0.04). Furthermore, 8-oxoGuo was positively associated with age (p=0.04) and negatively associated with thyrotropin (p=0.02). In the control group, the geometric mean of 8-oxoGuo was 1.23 nmol/mmol creatinine (95%CI:1.07-1.42), while 8-oxodG was 1.04 nmol/mmol creatinine (95%CI:0.88-1.23). Thus, compared with control subjects, euthyroid patients showed a significantly higher level of both 8-oxoGuo (p<0.001) and 8-oxodG (p=0.03). Conclusion: In hypothyroid women, no significant effect of levothyroxine treatment on the oxidative stress biomarkers 8-oxoGuo and 8-oxodG could be demonstrated. However, the excretion of these biomarkers was significantly higher than in healthy controls.